Hypertension affects more than 50 million people in the United States and is the most common disease for which adults seek medical attention. Studies of hypertension awareness, treatment, and control across ethnic groups indicate that significant disparities exist within the African-American and Hispanic communities compared to non-Hispanic Whites. Specifically, greater efforts are needed specifically to prevent and treat high blood pressure among African-Americans. While the prevalence of hypertension is lower in Hispanic communities, they have higher treated blood pressure than comparable White populations. To better understand the factors that effect control of blood pressure in hypertensives on antihypertensive therapies, we are taking advantage of a large cohort of hypertensives and their sibs with extensive clinical, social, behavioral, and genetic data from the Genetic Epidemiology Network of Arteriopathy (GENOA) study. It is well known that hypertensives respond heterogeneously to anti-hypertensive therapies, often requiring multiple medications to lower their blood pressure. This heterogeneity reflects a wide variety of factors that influence interindividual variation in the pharmacokinetic (i.e. mechanisms of drug absorption, distribution, metabolism, or excretion) or pharmacodynamic (i.e. biochemical and physiological mechanisms associated with the drug target) properties of a drug. Other factors including demographic, familial influences, socioeconomic factors and lifestyle factors are also expected to influence blood pressure treatment and control in hypertensives. Although this heterogeneity has long been established, relatively little is known about the specific social, behavioral, and genetic associations that influence ethnic variation in blood pressure response to anti-hypertensive drugs. We propose to comprehensively investigate the sources of variation in blood pressure levels in hypertensives from the general clinical population that reflect the wide spectrum of possible causes ranging from socio-demographic and lifestyle influences (Aim 1), their association with the distribution of hypertension duration and treatment regimes (Aim 2), the impact of risk factor-by-gene, gene-by-drug, or drug-by-risk factor interactions (Aim 3) in order to predict 5-year changes in blood pressure (Aim 4).